A Theory of Antibody—Antigen Reactions. I. Theory for Reactions of Multivalent Antigen with Bivalent and Univalent Antibody<sup>2</sup>

Goldberg, Richard J.

doi:10.1021/ja01142a045

Cited by 147 publications

(41 citation statements)

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“…Theoretical work by Goldberg and others provides equations that predict the quantity of antibody-antigen precipitate for given starting concentrations of antigen and antibody (9,10). However, these calculations embody a number of simplifying assumptions, such that all bonds are equal in strength and that intra-aggregate reactions yielding cyclical structures do not occur, that do not apply to small oligomeric clusters of proteins.…”

mentioning

confidence: 99%

Computer-based analysis of the binding steps in protein complex formation

Bray

Lay

1997

Proc. Natl. Acad. Sci. U.S.A.

109

111

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Computer models were used to examine whether and under what conditions the multimeric protein complex is inhibited by high concentrations of one of its components-an effect analogous to the prozone phenomenon in precipitin tests. A series of idealized simple ''ball-and-stick'' structures representing small oligomeric complexes of protein molecules formed by reversible binding reactions were analyzed to determine the binding steps leading to each structure. The equilibrium state of each system was then determined over a range of starting concentrations and K d s and the steady-state concentration of structurally complete oligomer calculated for each situation. A strong inhibitory effect at high concentrations was shown by any protein molecule forming a bridge between two or more separable parts of the complex. By contrast, proteins linked to the outside of the complex by a single bond showed no inhibition whatsoever at any concentration. Nonbridging, multivalent proteins in the body of the complex could show an inhibitory effect or not depending on the structure of the complex and the strength of its bonds. On the basis of this study, we suggest that the prozone phenomenon will occur widely in living cells and that it could be a crucial factor in the regulation of protein complex formation.In the precipitin reaction widely used by immunologists, increasing amounts of soluble antigen are added to a series of tubes each containing a fixed amount of antibody-containing serum. As the antigen increases, the quantity of precipitate also increases up to a maximum and then declines. The basis for this phenomenon, for which the term ''prozone'' was originally used (1, 2), is well understood and depends on the fact that the precipitates are made from a three-dimensional lattice of antigen and antibody molecules (3). Macroscopic precipitates form only when antibody and antigen are in optimal proportions, and if either molecule is present in excess, small soluble complexes are produced instead. With excess antigen, for example, the soluble complexes consist of antibody molecules surrounded by multiple molecules of antigen.There is reason to think that a similar effect may occur in the formation of multimeric protein complexes in living cells. Many if not most protein molecules in a living cell are part of multiprotein assemblies held together by noncovalent bonds, such as multimeric enzymes and receptor complexes (4-8). Such complexes have a definite structure and composition, and their formation depends in part on a series of diffusion-limited binding reactions influenced by the concentrations of participating protein molecules and their binding affinities for each other. Thus, if one species is present at much higher levels than the others, we might anticipate that something similar to the prozone phenomenon could operate. That is, we might find that formation of the structurally complete complex would be suppressed at the expense of smaller, incomplete clusters of proteins. Because the function of most protein com...

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mentioning

confidence: 99%

Computer-based analysis of the binding steps in protein complex formation

Bray

Lay

1997

Proc. Natl. Acad. Sci. U.S.A.

109

111

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“…Assuming that a single monolayer of BSA was formed over the particle surfaces, it is possible to conclude that the area occupied by each BSA molecule over the PVAc particles was equal to 5.2nm 2 , which is much lower than areas reported previously for BSA over other supports (from 35 to 44nm 2 ) [38][39][40]56] . This clearly indicates that multiple BSA layers (as many as seven) can be formed over the PVAc particles or that BSA molecules can interact with PVAc chains and penetrate (through mixing) in the particle.…”

Section: Adsorption Experimentsmentioning

confidence: 61%

“…Particularly, BSA has been used as a drug delivery agent, due to its capacity to bond covalently to different drugs [35][36][37] . BSA is a protein composed of 583 aminoacid residues, has molar mass of 66430g/gmol, is very soluble in water (it can be precipitated in high concentrations of a neutral salt, such as ammonium sulphate), has isoelectric point in the pH range of 4.60-5.70, and presents spheroidal shape, characteristic sizes of 4nm × 4nm × 14nm and Stoke radius of 3.48nm [38][39][40] . Lysozyme is another model biological molecule that finds many uses in the biotechnological and biomedical fields.…”

Section: Introductionmentioning

confidence: 99%

Adsorption of BSA (Bovine Serum Albuminum) and lysozyme on poly(vinyl acetate) particles

Santos¹,

Alves²,

Pinto³

2016

Polímeros

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SbstractPoly(vinyl acetate) (PVAc) particles find many uses in the biomedical field, including the use as particle embolizers. Particularly, embolizing particles can combine physical and chemical effects when they are doped with pharmaceuticals. For this reason, the adsorption of bovine serum albuminum (BSA) and lysozyme (used as model biomolecules) on PVAc particles produced through suspension polymerization is studied in the present manuscript in a broad range of pH values. It is shown that significant amounts of BSA and lysozyme can be adsorbed onto PVAc particles in the vicinities of the isoelectric point of the biomolecules (0.65mg of BSA and 1.0mg of lysozyme per g of PVAc), allowing for production of chemoembolizers through adsorption. Particularly, it is shown that lysozyme still presents residual activity after the adsorption process, which can constitute very important characteristic for real biomedical applications.

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“…The distribution of antigen/antibody complexes formed in the system at equilibrium is interpreted as being determined by concentrations of reactants and by their valencies (Goldberg, 1952(Goldberg, , 1953. This model has received some confirmation in virology through studies on tomato bushy stunt virus and its rabbit antiserum (Bradish & Crawford, 1960).…”

Section: Discussionmentioning

confidence: 99%

The Fixation of Complement by Virus-Antibody Complexes: Equivalence and Inhibition in the Reactions of the Viruses of Tomato Bushy Stunt and Foot-and-Mouth Disease with Rabbit and Guinea-Pig Antisera

Bradish

Jowett

Kirkham

1964

Journal of General Microbiology

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SUMMARYA sensitive and simply calculated complement-fixation test is described in which viral antigen and antibody react to completion for up to 90 min. a t 37' before the addition of one 70 yo haemolysis unit of complement. The test has been applied to reactions between the components of the virus system of foot-and-mouth disease, tomato bushy stunt virus, bovine plasma albumin and their rabbit or guinea-pig hyperimmune sera. In the restricted region of proportional fixation each pl. of complement represents about 3 x lo9 virus particles and 6 x loll molecules of albumin.In suspensions of foot-and-mouth disease virus of highest infectivity (1010 mouse ID50/ml.), probably less than 1 in 30 of the characteristic 25 mp particles are infective.Quantitative data define the regions of antibody excess, equivalence and antigen excess, and show that complement is bound as a secondary process to that of antigen/antibody complex formation, that complement is bound only by relatively massive complexes and that the independent formation of unrelated complexes in the same system may be sensitively detected. The location of the optimum reaction and the confirmation of equivalence allow fixation data to be related closely to parallel data on the neutralization of infectivity. Since the concentrations of antigen and of antibody for optimal fixation are almost independent, it is concluded that the maintenance of equivalence in terms of a constant antigen/antibody ratio is not a valid principle for the interpretation of such data.

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A Theory of Antibody—Antigen Reactions. I. Theory for Reactions of Multivalent Antigen with Bivalent and Univalent Antibody²

Cited by 147 publications

References 2 publications

Computer-based analysis of the binding steps in protein complex formation

Computer-based analysis of the binding steps in protein complex formation

Adsorption of BSA (Bovine Serum Albuminum) and lysozyme on poly(vinyl acetate) particles

The Fixation of Complement by Virus-Antibody Complexes: Equivalence and Inhibition in the Reactions of the Viruses of Tomato Bushy Stunt and Foot-and-Mouth Disease with Rabbit and Guinea-Pig Antisera

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A Theory of Antibody—Antigen Reactions. I. Theory for Reactions of Multivalent Antigen with Bivalent and Univalent Antibody2

Cited by 147 publications

References 2 publications

Computer-based analysis of the binding steps in protein complex formation

Computer-based analysis of the binding steps in protein complex formation

Adsorption of BSA (Bovine Serum Albuminum) and lysozyme on poly(vinyl acetate) particles

The Fixation of Complement by Virus-Antibody Complexes: Equivalence and Inhibition in the Reactions of the Viruses of Tomato Bushy Stunt and Foot-and-Mouth Disease with Rabbit and Guinea-Pig Antisera

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A Theory of Antibody—Antigen Reactions. I. Theory for Reactions of Multivalent Antigen with Bivalent and Univalent Antibody²